The completion of the total synthesis of deoxybouvardin and bouvardin (NSC 259968), unusual bicyclic hexapeptides possessing confirmed antitumor properties, the total synthesis of structurally-related agents, and the completion of cytotoxic, antitumor, and antimicrobial structure-activity studies including the evaluation of key partial structures are detailed. Extensions of the implemented methodology for peptide diaryl ether formation to the synthetic preparation of isodityrosine and total synthesis of 0F4949 I-IV (aminopeptidase inhibitors with confirmed antitumor and metastatic activity), K-13 (angiotensin I converting enzyme inhibitor) and piperazinomycin are detailed. New studies detailing the total synthesis of the naturally- occurring cyclic decapeptide antitumor-antibiotics luzopeptin -A, -B, -C, and E2 (BBM 928A-C, E2) and the initiation of cytotoxic, antitumor, and antimicrobial structure-activity studies are detailed. Additional studies designed to delineate the structural features of the naturally-occurring B-DNA bisintercalating agents which are responsible for or contribute to the agent B-DNA affinity and sequence-selectivity (bisintercalation and complementary peptide minor groove association) will be pursued.